CA2708570A1 - Composes organiques - Google Patents

Composes organiques Download PDF

Info

Publication number: CA2708570A1
Authority: CA; Canada
Prior art keywords: alkoxy; alkyl; substituted; unsubstituted; alk
Prior art date: 2007-12-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA2708570A

Other languages

English (en)

Inventor

Peter Herold

Robert Mah

Vincenzo Tschinke

Stjepan Jelakovic

Stefan Stutz

Dirk Behnke

Nathalie Jotterand

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2007-12-13

Filing date

2008-12-12

Publication date

2009-06-18

2008-12-12 Application filed by Individual filed Critical Individual

2009-06-18 Publication of CA2708570A1 publication Critical patent/CA2708570A1/fr

Status Abandoned legal-status Critical Current

Links

150000002894 organic compounds Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 144
150000003839 salts Chemical class 0.000 claims abstract description 69
238000000034 method Methods 0.000 claims abstract description 12
239000003814 drug Substances 0.000 claims abstract description 11
229910052770 Uranium Inorganic materials 0.000 claims abstract description 3
229910052721 tungsten Inorganic materials 0.000 claims abstract description 3
-1 3,4-dihydro-2H-benzo[1,4]oxazinyl Chemical group 0.000 claims description 116
229910052736 halogen Inorganic materials 0.000 claims description 25
150000002367 halogens Chemical group 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 12
206010020772 Hypertension Diseases 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000000850 2H-chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
229940002612 prodrug Drugs 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
206010019280 Heart failures Diseases 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
208000010412 Glaucoma Diseases 0.000 claims description 4
208000001647 Renal Insufficiency Diseases 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
208000033679 diabetic kidney disease Diseases 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
201000006370 kidney failure Diseases 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 3
125000004043 oxo group Chemical group O=* 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
230000002526 effect on cardiovascular system Effects 0.000 claims description 2
125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
229940127557 pharmaceutical product Drugs 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 8
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
229940079593 drug Drugs 0.000 abstract description 9
239000002461 renin inhibitor Substances 0.000 abstract description 6
238000002360 preparation method Methods 0.000 abstract description 5
229940086526 renin-inhibitors Drugs 0.000 abstract description 5
150000003053 piperidines Chemical class 0.000 abstract description 4
230000008569 process Effects 0.000 abstract description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
239000011541 reaction mixture Substances 0.000 description 52
239000000243 solution Substances 0.000 description 46
239000000203 mixture Substances 0.000 description 43
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
229910001868 water Inorganic materials 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
229910052938 sodium sulfate Inorganic materials 0.000 description 30
235000011152 sodium sulphate Nutrition 0.000 description 30
239000007832 Na2SO4 Substances 0.000 description 29
238000003818 flash chromatography Methods 0.000 description 29
239000003921 oil Substances 0.000 description 28
235000019198 oils Nutrition 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 26
239000012044 organic layer Substances 0.000 description 25
238000012360 testing method Methods 0.000 description 23
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 20
239000012267 brine Substances 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
230000000694 effects Effects 0.000 description 18
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 17
239000000126 substance Substances 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
238000000746 purification Methods 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
230000002829 reductive effect Effects 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
102000004190 Enzymes Human genes 0.000 description 11
108090000790 Enzymes Proteins 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
239000007858 starting material Substances 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
239000003112 inhibitor Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 9
VBZDXGATDYLXEZ-RXMQYKEDSA-N (2r)-3-methoxy-2-methylpropan-1-ol Chemical compound COC[C@H](C)CO VBZDXGATDYLXEZ-RXMQYKEDSA-N 0.000 description 8
HAKYKQWZRSPYAR-UHFFFAOYSA-N 2-(2-bromo-5-chlorophenyl)ethanol Chemical compound OCCC1=CC(Cl)=CC=C1Br HAKYKQWZRSPYAR-UHFFFAOYSA-N 0.000 description 8
101800000734 Angiotensin-1 Proteins 0.000 description 8
102400000344 Angiotensin-1 Human genes 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 8
229910000069 nitrogen hydride Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
DEDUBNVYPMOFDR-RXMQYKEDSA-N (2r)-2-ethoxypropan-1-ol Chemical compound CCO[C@H](C)CO DEDUBNVYPMOFDR-RXMQYKEDSA-N 0.000 description 7
101000579218 Homo sapiens Renin Proteins 0.000 description 7
239000002253 acid Substances 0.000 description 7
235000011114 ammonium hydroxide Nutrition 0.000 description 7
238000003556 assay Methods 0.000 description 7
238000001727 in vivo Methods 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
QIDYUGVQMSRSFY-UHFFFAOYSA-N 3-(2-bromo-5-chlorophenyl)propan-1-ol Chemical compound OCCCC1=CC(Cl)=CC=C1Br QIDYUGVQMSRSFY-UHFFFAOYSA-N 0.000 description 6
CODFXJPNZHQAQN-UHFFFAOYSA-N 4-bromo-3-(2-hydroxyethyl)phenol Chemical compound OCCC1=CC(O)=CC=C1Br CODFXJPNZHQAQN-UHFFFAOYSA-N 0.000 description 6
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
230000037396 body weight Effects 0.000 description 6
125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
JHPOQHHJQUTPCY-UHFFFAOYSA-N 2-[2-bromo-5-(3-methoxypropoxy)phenyl]ethoxy-tri(propan-2-yl)silane Chemical compound COCCCOC1=CC=C(Br)C(CCO[Si](C(C)C)(C(C)C)C(C)C)=C1 JHPOQHHJQUTPCY-UHFFFAOYSA-N 0.000 description 5
102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 5
108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 5
102100039205 Cytochrome P450 3A4 Human genes 0.000 description 5
108010029485 Protein Isoforms Proteins 0.000 description 5
102000001708 Protein Isoforms Human genes 0.000 description 5
241000700159 Rattus Species 0.000 description 5
108090000783 Renin Proteins 0.000 description 5
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000002585 base Substances 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
125000005647 linker group Chemical group 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
125000004430 oxygen atom Chemical group O* 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
239000000047 product Substances 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000000758 substrate Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 5
230000009261 transgenic effect Effects 0.000 description 5
238000011282 treatment Methods 0.000 description 5
CEVMYGZHEJSOHZ-UHFFFAOYSA-N 1-bromo-3-methoxypropane Chemical compound COCCCBr CEVMYGZHEJSOHZ-UHFFFAOYSA-N 0.000 description 4
NCRMNHSZPLHRRW-UHFFFAOYSA-N 2-iodoethoxy-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCI NCRMNHSZPLHRRW-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
102000005862 Angiotensin II Human genes 0.000 description 4
101800000733 Angiotensin-2 Proteins 0.000 description 4
108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 description 4
239000001828 Gelatine Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 4
239000012448 Lithium borohydride Substances 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
229910004679 ONO2 Inorganic materials 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
102100028255 Renin Human genes 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
CKKXJTUNHZUCKQ-UHFFFAOYSA-N [4-chloro-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]boronic acid Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(Cl)=CC=C1B(O)O CKKXJTUNHZUCKQ-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
229950006323 angiotensin ii Drugs 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
239000002775 capsule Substances 0.000 description 4
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
230000002255 enzymatic effect Effects 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
238000011835 investigation Methods 0.000 description 4
210000003734 kidney Anatomy 0.000 description 4
230000004060 metabolic process Effects 0.000 description 4
229960003793 midazolam Drugs 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
235000015320 potassium carbonate Nutrition 0.000 description 4
238000011533 pre-incubation Methods 0.000 description 4
125000003226 pyrazolyl group Chemical group 0.000 description 4
238000012216 screening Methods 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
235000017550 sodium carbonate Nutrition 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102100026533 Cytochrome P450 1A2 Human genes 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
125000005872 benzooxazolyl group Chemical group 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000013078 crystal Substances 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 3
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
239000008298 dragée Substances 0.000 description 3
230000036267 drug metabolism Effects 0.000 description 3
239000007850 fluorescent dye Substances 0.000 description 3
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 3
125000001041 indolyl group Chemical group 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
210000001853 liver microsome Anatomy 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
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230000003389 potentiating effect Effects 0.000 description 1
229960001289 prazosin Drugs 0.000 description 1
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000006410 propenylene group Chemical group 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
230000006920 protein precipitation Effects 0.000 description 1
201000001474 proteinuria Diseases 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
229940005657 pyrophosphoric acid Drugs 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
229960001404 quinidine Drugs 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
229960003147 reserpine Drugs 0.000 description 1
MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000005070 sampling Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910001415 sodium ion Inorganic materials 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
241000894007 species Species 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
150000003413 spiro compounds Chemical class 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
229960002256 spironolactone Drugs 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
QWCJHSGMANYXCW-UHFFFAOYSA-N sulfaphenazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=NN1C1=CC=CC=C1 QWCJHSGMANYXCW-UHFFFAOYSA-N 0.000 description 1
229960004818 sulfaphenazole Drugs 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000000948 sympatholitic effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229960001693 terazosin Drugs 0.000 description 1
VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
TZUBHLLUGBVNKN-IZEXYCQBSA-N tert-butyl (3s,4s)-3,4-dihydroxy-4-[4-(3-methoxypropoxy)-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]piperidine-1-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(OCCCOC)=CC=C1[C@]1(O)[C@@H](O)CN(C(=O)OC(C)(C)C)CC1 TZUBHLLUGBVNKN-IZEXYCQBSA-N 0.000 description 1
DDZMUZFKKCRQHX-IZEXYCQBSA-N tert-butyl (3s,4s)-4-[4-chloro-2-(2-hydroxyethyl)phenyl]-4-hydroxy-3-[[4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazin-6-yl]methoxy]piperidine-1-carboxylate Chemical compound C1([C@@]2(O)CCN(C[C@@H]2OCC2=CC=C3OCCN(C3=C2)CCCOC)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1CCO DDZMUZFKKCRQHX-IZEXYCQBSA-N 0.000 description 1
PEUQKGIFRGLMBK-IGKIAQTJSA-N tert-butyl (3s,4s)-4-[4-chloro-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-3,4-dihydroxypiperidine-1-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(Cl)=CC=C1[C@]1(O)[C@@H](O)CN(C(=O)OC(C)(C)C)CC1 PEUQKGIFRGLMBK-IGKIAQTJSA-N 0.000 description 1
CEWOYZBWCXGTQV-DFUITMLUSA-N tert-butyl (3s,4s)-4-[4-chloro-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-4-hydroxy-3-[[4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazin-6-yl]methoxy]piperidine-1-carboxylate Chemical compound C1([C@@]2(O)CCN(C[C@@H]2OCC2=CC=C3OCCN(C3=C2)CCCOC)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1CCO[Si](C(C)C)(C(C)C)C(C)C CEWOYZBWCXGTQV-DFUITMLUSA-N 0.000 description 1
GLFGKVBSNQTDRL-PUAPYOPTSA-N tert-butyl (3s,4s)-4-[4-chloro-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-4-hydroxy-3-[[4-(3-methoxypropyl)-3-oxo-1,4-benzoxazin-6-yl]methoxy]piperidine-1-carboxylate Chemical compound C1([C@@]2(O)CCN(C[C@@H]2OCC2=CC=C3OCC(=O)N(C3=C2)CCCOC)C(=O)OC(C)(C)C)=CC=C(Cl)C=C1CCO[Si](C(C)C)(C(C)C)C(C)C GLFGKVBSNQTDRL-PUAPYOPTSA-N 0.000 description 1
ICZCUMCAZACFDR-SHUZPENHSA-N tert-butyl (3s,4s)-4-hydroxy-4-[2-(2-hydroxyethyl)-4-(3-methoxypropoxy)phenyl]-3-[[4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazin-6-yl]methoxy]piperidine-1-carboxylate Chemical compound OCCC1=CC(OCCCOC)=CC=C1[C@]1(O)[C@@H](OCC=2C=C3N(CCCOC)CCOC3=CC=2)CN(C(=O)OC(C)(C)C)CC1 ICZCUMCAZACFDR-SHUZPENHSA-N 0.000 description 1
GFICZBDHMLDMIS-XKKDUZJHSA-N tert-butyl (3s,4s)-4-hydroxy-4-[4-(3-methoxypropoxy)-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-3-[[4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazin-6-yl]methoxy]piperidine-1-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(OCCCOC)=CC=C1[C@]1(O)[C@@H](OCC=2C=C3N(CCCOC)CCOC3=CC=2)CN(C(=O)OC(C)(C)C)CC1 GFICZBDHMLDMIS-XKKDUZJHSA-N 0.000 description 1
HHXRSVWNDGBWED-UHFFFAOYSA-N tert-butyl 4-[4-(3-methoxypropoxy)-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(OCCCOC)=CC=C1C1=CCN(C(=O)OC(C)(C)C)CC1 HHXRSVWNDGBWED-UHFFFAOYSA-N 0.000 description 1
JHAIUIFCJBOGGP-UHFFFAOYSA-N tert-butyl 4-[4-chloro-2-[2-tri(propan-2-yl)silyloxyethyl]phenyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(Cl)=CC=C1C1=CCN(C(=O)OC(C)(C)C)CC1 JHAIUIFCJBOGGP-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000001583 thiepanyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
229960004605 timolol Drugs 0.000 description 1
229940110851 tolazine Drugs 0.000 description 1
JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000011824 transgenic rat model Methods 0.000 description 1
229960003741 tranylcypromine Drugs 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
229960001288 triamterene Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000036325 urinary excretion Effects 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
229960001722 verapamil Drugs 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Diabetes (AREA)
Ophthalmology & Optometry (AREA)
Vascular Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA2708570A 2007-12-13 2008-12-12 Composes organiques Abandoned CA2708570A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP07150019.3		2007-12-13
EP07150019		2007-12-13
PCT/EP2008/067407 WO2009074674A2 (fr)	2007-12-13	2008-12-12	Composés organiques

Publications (1)

Publication Number	Publication Date
CA2708570A1 true CA2708570A1 (fr)	2009-06-18

Family

ID=39709362

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2708570A Abandoned CA2708570A1 (fr)	2007-12-13	2008-12-12	Composes organiques

Country Status (12)

Country	Link
US (1)	US20110009399A1 (fr)
EP (1)	EP2231677A2 (fr)
JP (1)	JP2011506401A (fr)
KR (1)	KR20100097731A (fr)
CN (1)	CN101896490A (fr)
AR (1)	AR069677A1 (fr)
AU (1)	AU2008334555A1 (fr)
BR (1)	BRPI0819920A2 (fr)
CA (1)	CA2708570A1 (fr)
EA (1)	EA201000889A1 (fr)
TW (1)	TW200940547A (fr)
WO (1)	WO2009074674A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2243779A4 (fr)	2007-12-19	2011-04-20	Dainippon Sumitomo Pharma Co	Dérivé hétérocyclique bicyclique
EP2447264A4 (fr)	2009-06-24	2012-12-12	Dainippon Sumitomo Pharma Co	Dérivé amino cyclique n-substitué
US20120202837A1 (en) *	2009-10-13	2012-08-09	Austin Chen	Spirocyclic piperidine derivatives useful as renin inhibitors

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW200513461A (en) *	2003-10-01	2005-04-16	Speedel Experimenta Ag	Organische verbindungen
KR100974967B1 (ko) *	2005-07-14	2010-08-09	에프. 호프만-라 로슈 아게	Ｖ1ａ 수용체 길항물질로서의인돌-3-카본일-스피로-피페리딘 유도체

2008
- 2008-12-11 TW TW097148138A patent/TW200940547A/zh unknown
- 2008-12-12 WO PCT/EP2008/067407 patent/WO2009074674A2/fr active Application Filing
- 2008-12-12 US US12/745,960 patent/US20110009399A1/en not_active Abandoned
- 2008-12-12 AU AU2008334555A patent/AU2008334555A1/en not_active Abandoned
- 2008-12-12 CA CA2708570A patent/CA2708570A1/fr not_active Abandoned
- 2008-12-12 KR KR1020107015329A patent/KR20100097731A/ko not_active Application Discontinuation
- 2008-12-12 JP JP2010537459A patent/JP2011506401A/ja active Pending
- 2008-12-12 BR BRPI0819920-5A patent/BRPI0819920A2/pt not_active IP Right Cessation
- 2008-12-12 EA EA201000889A patent/EA201000889A1/ru unknown
- 2008-12-12 AR ARP080105411A patent/AR069677A1/es unknown
- 2008-12-12 CN CN2008801207312A patent/CN101896490A/zh active Pending
- 2008-12-12 EP EP08859256A patent/EP2231677A2/fr not_active Withdrawn

Also Published As

Publication number	Publication date
EA201000889A1 (ru)	2011-02-28
US20110009399A1 (en)	2011-01-13
AU2008334555A1 (en)	2009-06-18
JP2011506401A (ja)	2011-03-03
WO2009074674A3 (fr)	2009-07-30
WO2009074674A2 (fr)	2009-06-18
EP2231677A2 (fr)	2010-09-29
CN101896490A (zh)	2010-11-24
KR20100097731A (ko)	2010-09-03
BRPI0819920A2 (pt)	2015-05-19
TW200940547A (en)	2009-10-01
AR069677A1 (es)	2010-02-10

Legal Events

Date	Code	Title	Description
2013-02-06	FZDE	Discontinued	Effective date: 20121212

Publication	Publication Date	Title
WO2006103277A2 (fr)	2006-10-05	Piperidines substituees
CA2708570A1 (fr)	2009-06-18	Composes organiques
CA2702745A1 (fr)	2009-04-23	Piperidines trisubstituees
EP1908471A1 (fr)	2008-04-09	Tétrahydropyridines comme inhibiteurs de la renine
CA2703593A1 (fr)	2009-04-30	Piperidines 4,4-disubstituees
US8003640B2 (en)	2011-08-23	Organic compounds
US20100267713A1 (en)	2010-10-21	4,4-disubstituted piperidines
US8022068B2 (en)	2011-09-20	Substituted piperidines as renin inhibitors
AU2009211378A1 (en)	2009-08-13	Substituted piperidines as renin inhibitors
EP1908763A1 (fr)	2008-04-09	Composés bicycliques
EP1897879A2 (fr)	2008-03-12	Pipéridines 2,4,5 substituées comme inhibiteurs de la rénine